Background: The indirect comparison of two interventions can be valuable in many situations. However, the quality of an indirect comparison will depend on several factors including the chosen methodology and validity of underlying\ud assumptions. Published indirect comparisons are increasingly more common in the medical literature, but as yet, there are no published recommendations of how they should be reported. Our aim is to systematically review the quality of published indirect comparisons to add to existing empirical data suggesting that improvements can be made when reporting and applying indirect comparisons.\ud \ud Methodology/Findings: Reviews applying statistical methods to indirectly compare the clinical effectiveness of two\ud interventions using randomised controlled trials were eligible. We searched (1966–2008) Database of Abstracts and Reviews of Effects, The Cochrane library, and Medline. Full review publications were assessed for eligibility. Specific criteria to assess quality were developed and applied. Forty-three reviews were included. Adequate methodology was used to calculate the indirect comparison in 41 reviews. Nineteen reviews assessed the similarity assumption using sensitivity analysis, subgroup analysis, or meta-regression. Eleven reviews compared trial-level characteristics. Twenty-four reviews assessed statistical\ud homogeneity. Twelve reviews investigated causes of heterogeneity. Seventeen reviews included direct and indirect evidence for the same comparison; six reviews assessed consistency. One review combined both evidence types. Twentyfive reviews urged caution in interpretation of results, and 24 reviews indicated when results were from indirect evidence by stating this term with the result.\ud Conclusions: This review shows that the underlying assumptions are not routinely explored or reported when undertaking indirect comparisons. We recommend, therefore, that the quality of indirect comparisons should be improved, in particular, by assessing assumptions and reporting the assessment methods applied. We propose that the quality criteria applied in this article may provide a basis to help review authors carry out indirect comparisons and to aid appropriate interpretation.

17. Abou-Setta AM (2007) What is the best site for embryo deposition? A systematic review and meta-analysis using direct and adjusted indirect comparisons. Reproductive Biomedicine Online 14(5): 611-9.

18. Berner MM, Kriston L, Harms A (2006) Efficacy of PDE-5-inhibitors for erectile dysfunction. A comparative meta-analysis of fixed-dose regimen randomized controlled trials administering the International Index of Erectile Function in broad-spectrum populations. International Journal of Impotence Research 18(3): 229-35.

30. Habib AS, El-Moalem HE, Gan TJ (2004) The efficacy of the 5-HT3 receptor antagonists combined with droperidol for PONV prophylaxis is similar to their combination with dexamethasone. A meta-analysis of randomized controlled trials. Canadian Journal of Anaesthesia 51(4): 311-9.

38. McAlister FA, Stewart S, Ferrua S, McMurray JJ (2004) Multidisciplinary strategies for the management of heart failure patients at high risk for admission: a systematic review of randomized trials. Journal of the American College of Cardiology 44(4): 810-819.